The hypophysiotropic neurons form the final common pathway for the regulation of the function of the anterior pituitary and they receive inputs from other neurons through synaptic connections. Blood-born substances from the peripheral endocrine organs may also modify the activity of hypophysiotropic neurons by acting through their specific receptors on hypophysiotropic neurons. Our major goal is to identify these connections and receptors at the light and electron microscopic levels. During the last year, we have shown that, within the arcuate nucleus, galanin neurons form an intranuclear circuitry by which galanin regulates its own release via a negative ultrashort-loop feedback mechanism. Galanin, possibly from the arcuate nucleus, innervates hypophysiotropic somatostatin neurons in the anterior periventricular nucleus. Through this innervation, galanin can modify the activity of somatostatin neurons, and indirectly, growth hormone secretion from the pituitary. These observations reinforce the notion that galanin shares with other classic hypophysiotropic hormones the ability to regulate the firing rate of its own neuronal network. We have also used an immortalized LHRH cell line from transgenic mice for these studies. Our electron microscopic analysis indicates that the LHRH cell line has morphological characteristics similar to the in vivo LHRH neurons, and these cells form extensive synaptic connections with each other providing a morphological basis for a synchronized secretory activity. LHRH cells implanted into the brain of intact animals contact fenestrated capillaries of the median eminence, thus providing the morphological evidence for active hormone release into the portal circulation. These immortalized neurons in vitro establish connections with pituitary cells in culture, indicating that secretory products of the anterior pituitary can direct axonal growth.